Brachytherapy (from the Greek word brachys, meaning “short-distance”), also known as internal radiotherapy, sealed source radiotherapy, curietherapy or endocurietherapy, is a form of radiotherapy where a radiation source is placed inside or next to the area requiring treatment. Brachytherapy is commonly used as an effective treatment for cervical, prostate, breast, and skin cancer and can also be used to treat tumors in many other body sites.
Different types of brachytherapy can be defined according to (1) the placement of the radiation sources in the target treatment area, (2) the rate or ‘intensity’ of the irradiation dose delivered to the tumor, and (3) the duration of dose delivery. The two main types of brachytherapy treatment in terms of the placement of the radioactive source are interstitial and contact. In the case of interstitial brachytherapy, the sources are placed directly in the target tissue of the affected site, such as the prostate or breast. Contact brachytherapy involves placement of the radiation source in a space next to the target tissue. This space may be a body cavity (intracavitary brachytherapy) such as the uterus or vagina; a body lumen (intraluminal brachytherapy) such as the trachea or oesophagus; or externally (surface brachytherapy), such as the skin. A radiation source can also be placed in blood vessels (intravascular brachytherapy) for the treatment of coronary in-stent restenosis.
The dose rate of brachytherapy refers to the level or ‘intensity’ with which the radiation is delivered to the surrounding medium and is expressed in Grays per hour (Gy/h). Low-dose rate (LDR) brachytherapy involves implanting radiation sources that emit radiation at a rate of up to 2 Gy·h−1. Medium-dose rate (MDR) brachytherapy is characterized by a medium rate of dose delivery, ranging between 2 Gy·h−1 to 12 Gy·h−1. High-dose rate (HDR) brachytherapy is when the rate of dose delivery exceeds 12 Gy·h−1, and is commonly used for in tumors of the cervix. Pulsed-dose rate (PDR) brachytherapy involves short pulses of radiation.
Brachytherapy is commonly used in the treatment of early or locally confined cervical cancer and is a standard of care in many countries. Cervical cancer can be treated with LDR, PDR or HDR brachytherapy. The chances of staying free of disease (disease-free survival) and of staying alive (overall survival) are similar for LDR, PDR and HDR treatments. However, a key advantage of HDR treatment is that each dose can be delivered on an outpatient basis with a short administration time, providing greater convenience for many patients. In fact, a 2005 survey by the American Brachytherapy Society (ABS) reported that two-thirds of the responding medical providers performed HDR-VBT, and more than 90% of those providers used a single channel vaginal cylinder as the applicator.
Although a popular treatment modality, one of the difficulties with any kind of HDR brachytherapy is that even small errors in positioning can have serious side effects due to the high doses involved. Using endometrial cancer as an example, we will now demonstrate the scope of the problem.
An ABS panel in 2000 provided specific guidelines for HDR applicator selection, insertion techniques, target volume definition, and dose fractionation, among others. The ABS panel recommended that for HDR-VBT, the largest diameter applicator should be selected to ensure close mucosal apposition and to eliminate “air gaps.” The panel also recommended, among other things, that (1) the treatment plan should be optimized to conform to the target volume whenever possible while recognizing the limitations of computer optimization, (2) the anisotropic correction should be included in the dose calculation and the optimization points should be placed at the apex (where the majority of the disease is located) and along the curved portion of the cylinder dome in addition to the lateral vaginal mucosa, (3) the dose prescription point should be clearly specified either at the surface or at a 0.5 cm depth (margin), and (4) the dose should be reported both at the vaginal surface and at the 0.5 cm depth, regardless of the dose prescription point.
The 0.5 cm depth treatment protocol has limitations. The use of the depth specification creates a treatment margin to account for applicator and/or patient motion, ensuring that the disease is covered and biochemical failure is avoided. Unfortunately, a corresponding dose is disadvantageously applied. Ideally, a “surface dose” method would be employed with the dose deposited at the surface of the cylinder. However, such a method has proven inadequate, because although the healthy tissue dose becomes negligible, a less than adequate dose is delivered to the target area.
Although the cylinder is the applicator of choice, it has limitations. It is well established that the 1 mm of tissue surrounding the cylinder is the predominant location of the disease. To deliver an appropriate dose to this area, the treatment device must be in direct contact with the vaginal surface. Any obstruction, such as an air pocket occurring between the treatment device and the mucosa, displaces the mucosa away from the dose, resulting in a cold spot or dose reduction to the target. In addition, the presence of air gaps sometimes moves the applicator within the vagina, so that the clinical target volume (CTV) is disadvantageously no longer equivalent to the planning target volume (PTV).
The standard dose protocol typically assumes no air pockets, and proper applicator location. An air pocket creates separation between applicator and mucosa. The separation can displace the target outside of the dose range. This could lead to all, or a portion, of the target displaced outside of the 0.5 cm prescription.
The effects of air pockets on dose delivery have been well documented in recent medical studies. In one such study, the authors of the study determined that 32% of the patients in their study had an air pocket larger then 2 mm, with the median number of air pockets per patient being one pocket. In another study of 25 patients with daily CT scans during treatment, 20 (80%) had one or more air pockets present in the upper vagina in at least one of their six treatment fractions. The total number of air pockets found throughout treatment for all 25 patients was 90 pockets (60% of treatments). The result was a disadvantageous average dose reduction of 27%.
Other factors, such as applicator positioning, can also have a clinically significant impact on dose delivery. Improper applicator angle can result in increased toxicity and reduced dose to the target. One medical study investigated the effect of the cylinder tilt on the sensitive structure volumes, and suggested simulation of the applicator position before each fraction.
The ABS recommended in 2000 that single-fraction planning was acceptable as long as the geometry of the implant remained the same for every insertion. However, a paradigm shift is emerging in brachytherapy whereby all treatments are becoming image guided, and all fractions are imaged regardless of the implant type. These findings indicate that scanning only the first fraction of a patient's treatment is insufficient for determining vaginal mucosa conformity to the cylinder throughout the course of treatment. Therefore, the findings indicate that to obtain an accurate and complete geometric dosimetric assessment of the patient's treatment, the patient should be imaged for every treatment fraction.
Thus, it is readily apparent that positioning of the applicator is of critical importance during HDR brachytherapy, in order to maximize its effectiveness and minimize its side effects. Current methodology uses gauze packing, as it is a simple and inexpensive method of positioning the applicator. However inexpensive, neither patients nor practitioners like gauze packing as it is neither comfortable, nor easy to implement and achieve consistent positioning.
Latex balloons have been developed to use in place of the gauze. However, all of the prior art balloons are non-conforming—that is they do not hold their shape when squeezed. Such balloons are an improvement over gauze, but still allow for considerable slop in treatment margins because the balloon is easily deformed under pressure and body cavities are a mobile environment. Further, while latex is inexpensive to mold, it is allergenic and many patients cannot use it.
Other solutions employ rigid intracavitary cylinders, which are certainly conforming. However, these have no capacity to adapt to patient-specific anatomy or motion, and are less than comfortable to use.
Therefore, a need exists to eliminate air pockets during HDR brachytherapy, regardless of which bodily orifice is being treated. A need also exists to eliminate the adverse effect of improper applicator angle during HDR brachytherapy. The ideal solution would allow some amount of flexibility, so that patient anatomy and comfort can be accommodated, but would still be conforming, that is hold its shape under in the constrained environment inside the body. The ideal balloon would also be adaptable for use in other body cavities, such as the rectum or oesophagus, and would be capable of use with either single channel or multi-channel applicators, and thus be of universal applicability in hospital settings, regardless of which type of applicator is available.